Project Summary The Hematologic Malignancies (HM) Program, which received ?Outstanding to Exceptional? merit in the 2010 CCSG renewal, was established in 1994 to translate basic scientific discoveries into novel therapeutics for patients with myeloid and lymphoid neoplasms. The Program has two scientific aims. They are to: 1) Develop a mechanisms-based understanding of the genetic, cellular, and biochemical processes regulating normal and malignant hematopoiesis, and 2) Translate basic scientific discoveries into more effective and manageable therapies. Thematic areas include transcriptional, translational, and epigenetic regulation of normal and malignant hematopoietic cells; signal transduction in normal and malignant hematopoietic cells; molecular therapeutics; hematopoietic stem cell biology and transplantation; and immune-based therapies. Program members are extensive users of CCSG-supported resources (e.g., Clinical Protocol and Data Management, Biostatistics Core, Clinical Cell and Vaccine Production Facility, Flow Cytometry and Cell Sorting Facility, and Human Immunology Core) and have extensive collaborations with other Abramson Cancer Center Programs including Cancer Control, Cancer Therapeutics, Immunobiology, Melanoma and Cutaneous Malignancies, Radiobiology and Imaging, and Pediatric Oncology. The Program is Co-Led by Dr. Edward Stadtmauer, an expert in clinical trials of novel therapeutics for hematologic malignancies and bone marrow transplantation, and Dr. Nancy Speck, an internationally known basic scientist working in the area of hematopoietic stem cells and leukemia. The Program's 21 members come from five departments (Medicine, Pediatrics, Genetics, Pathology and Laboratory Medicine, and Cell and Developmental Biology) in the Perelman School of Medicine. An innovative Hematologic Malignancies Translational Center of Excellence co-led by Dr. Stadtmauer has catalyzed an already successful Program by adding laboratory, tissue banking, and clinical research personnel resources as well as pilot grant funding. Prominent examples of Program advances include the demonstration by Dr. Blobel that the formation of chromatin loops directly activates transcription of globin genes, the demonstration by Dr. Tong that interaction of the cytokine signaling regulator Lnk with JAK2 is regulated by the 14-3-3 proteins, the reduction of graft versus host disease by CCR5 blockade, reported by a new member, Dr. Reshef and colleagues, and the application of Chimeric Antigen Receptor (CAR) modified T-cell therapy for CLL and B-cell ALL, led by Dr. Porter. Weekly seminars, collaborative grant submissions, weekly clinical working group meetings, and an annual research retreat organized by Drs. Speck and Stadtmauer facilitate member interactions. Currently, members have research funding totaling $6.7M (annual direct costs) of which $5M is peer-reviewed and $2.4M is from the NCI. During the project period, members published 358 cancer- relevant publications, of which 18% were intra-Programmatic, 20% were inter-Programmatic and 64% were multi-institutional.